title: Inhibitory effects of a cationic liposome on allergic reaction mediated by mast cell activation.
abstract: Several studies have shown that cationic liposomes exert immunomodulatory effects with low immunogenicity and toxicity, and offer advantages such as easy preparation and targeting. Cationic liposomes not only transport DNA to immune cells but also enhance the function of antigen presenting cells such as dendritic cells and macrophages. Here, we investigated the effect of a particular cationic liposome on mast cell function during allergic reaction. We found that the cationic liposomes bound to the mast cell surface suppressed degranulation induced by cross-linking of high affinity immunoglobulin E receptors in a time- and dose-dependent manner. The suppression of degranulation was mediated by impairment of the sustained level of intracellular Ca(2+) concentration ([Ca(2+)]i) derived from the inhibition of store-operated Ca(2+) entry. The decrease in sustained elevation of [Ca(2+)]i led to the suppression of phosphorylation of soluble N-ethylmaleimide-sensitive factor attachment protein receptor proteins such as SNAP-23, syntaxin-4, which are necessary for membrane fusion between secretory granules and the plasma membrane during degranulation. Furthermore, the cationic liposomes suppressed vascular permeability elevation induced by mast cell activation in mice. These results showed that cationic liposomes possess the novel property of inhibiting mast cell activation, suggesting the possibility of developing cationic liposomes as anti-allergic effectors.
authors.affiliation: School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya 464-8650, Japan. Electronic address: inoh@dpc.agu.ac.jp.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Inoh
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tadokoro
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tanabe
authors.forename: Makoto
authors.initials: M
authors.lastname: Inoue
authors.forename: Naohide
authors.initials: N
authors.lastname: Hirashima
authors.forename: Mamoru
authors.initials: M
authors.lastname: Nakanishi
authors.forename: Tadahide
authors.initials: T
authors.lastname: Furuno
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002199:Capillary Permeability; D002412:Cations; D015550:Cell Degranulation; D002460:Cell Line; D006967:Hypersensitivity / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D008081:Liposomes; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats
chemical_list: D002412:Cations; D008081:Liposomes; D002118:Calcium
keywords: Allergy; Calcium; Cell signaling; Liposome